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Understanding the Causes of Pseudoexfoliation Glaucoma

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Pseudoexfoliation (PEX) glaucoma is notable for the fluffy white deposits clinicians observe on lens surfaces. While this dandruff-like material gives PEX glaucoma a distinctive diagnostic feature, it is unknown what drives the disease. To better understand PEX glaucoma’s underlying causes, researchers at the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine recently used cutting-edge metabolomic studies to identify molecules that contribute to PEX pathology. Their work was published in the journal Molecular Omics.

“By determining the metabolic changes occurring in the eye during this vision-threatening disease process, we may be better able to understand how these proteins are affecting the eye, causing damage, and leading to permanent and irreversible blindness,” said Sanjoy Bhattacharya, PhD, professor of ophthalmology and senior author on the paper. “From there, we can study the molecular targets in this type of glaucoma and hopefully develop treatments.”

To learn more about PEX glaucoma’s biology, the team used highly sensitive mass spectrometry to examine eye water for PEX metabolites — small molecules produced when larger ones are broken down (metabolized). Because these molecules can be biologically active, identifying them is an important step toward understanding how the disease occurs and researching new, targeted drug therapies.

Mass spectrometry produces massive data sets that are complex to manage and interpret. The Bascom Palmer team applied artificial intelligence to condense the data and help them to understand the results — a new approach to metabolomic discovery. The researchers performed these studies on 3 groups: individuals with normal eyes, patients with primary open-angle glaucoma, and patients with PEX glaucoma. While there were many commonalities, the scientists found significantly different metabolite signatures in each type of glaucoma, including 125 metabolites unique to PEX glaucoma. Of these, 11 warranted further study.

“If we know which particular metabolites are deleterious and dysregulated, we can potentially target and customize molecular therapy to treat or even cure this eye disease to protect and save vision,” said Richard K. Lee, MD, PhD, associate professor and the Walter G. Ross Chair of Ophthalmology, a coauthor on the study.